Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan.
Neurosci Lett. 2013 Sep 13;551:39-42. doi: 10.1016/j.neulet.2013.07.006. Epub 2013 Jul 16.
Nesfatin-1 is a neuropeptide localized in hypothalamic paraventricular nucleus (PVN). Previously, we have reported the mechanism of feeding suppression by nesfatin-1, and also reported the ability of nesfatin-1 in regulating stress response and the circadian feeding pattern. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide also related to the stress response, feeding, and regulation of cardiovascular and autonomic nervous systems. The neurons with receptors for PACAP are distributed in PVN. However, there are no reports showing the direct effect of PACAP on nesfatin-1 neurons. In order to explore the direct effect of PACAP on PVN nesfatin-1 neuron, we have measured the cytosolic free calcium ([Ca(2+)]i) using fura-2 microfluorometry in single neurons isolated from PVN of adult rats, followed by immunocytochemical identification of nesfatin-1 neurons. PACAP at 10(-15)M to 10(-9)M increased [Ca(2+)]i in dose dependent manner. PAC1 and VPAC2 receptor agonists also increased [Ca(2+)]i. Sixteen out of 40 neurons (40%) in PVN responded to 10(-9)M PACAP, and 12 out of 16 neurons (75%) which responded to 10(-9)M PACAP were found to be nesfatin-1 neurons. In this paper we show that PACAP directly activates nesfatin-1 neurons in PVN. The data suggest that nesfatin-1 controls feeding, stress response or autonomic response under PACAP regulation.
nesfatin-1 是一种定位于下丘脑室旁核（PVN）的神经肽。先前，我们已经报道了 nesfatin-1 抑制摄食的机制，还报道了 nesfatin-1 调节应激反应和昼夜摄食模式的能力。垂体腺苷酸环化酶激活肽（PACAP）是一种与应激反应、摄食以及心血管和自主神经系统调节有关的神经肽。具有 PACAP 受体的神经元分布在 PVN 中。然而，目前尚无报道显示 PACAP 对 nesfatin-1 神经元有直接作用。为了探讨 PACAP 对 PVN nesfatin-1 神经元的直接作用，我们使用 fura-2 微荧光法测量了从成年大鼠 PVN 分离的单个神经元中的细胞浆游离钙（[Ca(2+)]i），随后通过 nesfatin-1 神经元的免疫细胞化学鉴定。10(-15)M 至 10(-9)M 的 PACAP 呈剂量依赖性增加 [Ca(2+)]i。PAC1 和 VPAC2 受体激动剂也增加了 [Ca(2+)]i。PVN 中的 40 个神经元中有 16 个（40%）对 10(-9)M PACAP 有反应，而在对 10(-9)M PACAP 有反应的 16 个神经元中有 12 个（75%）是 nesfatin-1 神经元。本文我们表明，PACAP 直接激活 PVN 中的 nesfatin-1 神经元。数据表明，nesfatin-1 在 PACAP 调节下控制摄食、应激反应或自主反应。
